Seasonal variation in consumption and plasma concentrations of fatty acids in Japanese female dietitians

Objective: To study seasonal variation in intake and plasma concentrations of fatty acids (FAs) in Japanese female dietitians. Subjects and methods: We assessed consumption of FAs based on four season 7 consecutive day weighed diet records from 71 Japanese female dietitians in 1996–1997. Using overnight fasting venous blood, plasma concentrations of FAs were analyzed by gas chromatography. Seasonal variation in consumption and plasma concentrations was examined by ANOVA for repeated values, followed by Tukey's multiple t-test. We calculated Spearman's partial rank correlation coefficients (CCs) between intake and plasma concentrations of FAs. Furthermore, we computed inter-seasonal Spearman's partial rank CCs for consumption and plasma concentrations of FAs. Results: Statistically significant seasonal differences were observed in consumption for most FAs, except for myristic acid, monounsaturated FAs, oleic acid, n-6 polyunsaturated FAs (PUFAs), linoleic acid, -linolenic acid, -linolenic acid, PUFAs/saturated FAs, and n-6 PUFAs/n-3 PUFAs, and for most plasma concentrations, except for stearic acid, -linolenic acid, n-3 PUFAs, -linolenic acid, eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and n-3 highly unsaturated FAs (HUFAs). However, statistically significant Spearman's partial rank CCs between intake and plasma concentrations were observed for EPA, DHA, n-3 HUFAs, n-6 PUFAs/n-3 PUFAs and n-6 PUFAs/n-3 HUFAs for almost all seasons. Conclusions: Seasonal variation exists in consumption and plasma concentrations of FAs, so that this should be taken into account in epidemiological analyses, including case–control and cohort studies.     

The effects of clonidine premedication on the blood pressure and tachycardiac responses to ephedrine in elderly and young patients during propofol anesthesia

We studied the pressor and tachycardiac responses to ephedrine in elderly and young patients given either clonidine or midazolam during propofol anesthesia. In the first experiment, elderly (>60 yr) and young (20-45 yr) patients were randomly allocated to one of four groups according to age and premedicated regimens (n = 16 each; elderly-clonidine [EC], elderly-midazolam [EM], young-clonidine [YC], and young-midazolam [YM]). Under propofol anesthesia, ephedrine was injected, and hemodynamic measurements were made. In the second experiment, with clonidine premedication, elderly patients (n = 16) were given a reduced dose of propofol (EC-LP) and young patients (n = 16) were given an increased dose of propofol (YC-HP). Ephedrine was injected, and he- modynamic measurements were performed. The in-creases in mean blood pressure and heart rate were larger in the EC group than in the EM, YM, and EC-LP groups (P < 0.05). In the YC-HP group, the pressor response to ephedrine tended to be augmented as compared with the YC group but was not statistically significant. These results suggest that clonidine premedication augmented the pressor and tachycardiac responses to ephedrine, especially in elderly patients during a standard dose of propofol anesthesia, and that clonidine, age, and propofol could be involved in the augmentation of the blood pressure and tachycardiac responses to ephedrine. IMPLICATIONS: Clonidine premedication augments the pressor and tachycardiac responses to ephedrine in elderly patients during standard or large doses of propofol anesthesia but does not augment during small doses of propofol anesthesia. Clonidine, age, and propofol could be involved in the augmentation of the pressor and tachycardiac responses to ephedrine.     

The impact of donor chemical overdose on the outcome of liver transplantation

BACKGROUND: To overcome the critical shortage of liver grafts, many centers have been widening the acceptance criteria for liver donation. Use of liver grafts from victims who have suffered chemical overdose (COD) may be one option that could help to expand the donor pool. However, this practice has been poorly documented. METHODS: Of 1,195 orthotopic liver transplantations performed at our institution between June 1994 and March 2001, 22 involved livers (1.8%) were retrieved from COD donors. Donor and recipient characteristics and posttransplantation outcomes were analyzed retrospectively. RESULTS: The main chemicals causing brain death of the donor were carbon monoxide (n=4), cocaine (n=4), tricyclic antidepressants (n=3), 3,4-methylenedioxy- methamphetamine (n=2), opiates (n=2), aspirin (n=1), gamma hydroxybutyrate (n=1), heroin (n=1), insulin (n=1), verapamil (n=1), barbiturate (n=1), and brompheniramine/phenylpropanolamine (n=1). Primary nonfunction developed in one patient who had received a liver from an 3,4-methylenedioxymethamphetamine-intoxicated donor. Another patient died of fungal meningitis 10 days after transplantation with a functioning graft. The remaining 20 patients experienced acceptable early graft function, as demonstrated by initial mean peak values of bilirubin (4.8 mg/dL), aspartate aminotransferase (624 U/L), and alanine aminotransferase (730 U/L). One-year graft survival rate estimated by the Kaplan-Meier method was 86%. CONCLUSIONS: Satisfactory outcomes of graft function were achieved in orthotopic liver transplantations from COD donors. The cautious use of liver grafts from selected COD donors may be a worthwhile method of increasing the availability of scarce donor organs.     

Modiolides A and B,two new 10-membered macrolides from a marine-derived fungus

Two new 10-membered macrolides, modiolides A (1) and B (2), and a new linear pentaketide, modiolin (3), were isolated from the cultured broth of a fungus Paraphaeosphaeria sp. (N-119), which was separated from a marine horse mussel, and the structures were elucidated by spectroscopic data.     

Biological activity of persimmon (Diospyros kaki) peel extracts

Fractionated extracts of persimmon (Diospyros kaki) peels were studied for cytotoxic activity, multidrug resistance (MDR) reversal activity, anti-human immunodeficiency virus (HIV) activity and anti-Helicobacter pylori (H. pylori) activity. The potent cytotoxic activity against human oral squamous cell carcinoma cells (HSC-2) and human submandibular gland tumor (HSG) cells was found in the acetone fractions (A4 and A5) with IC(50) ranging from 21 to 59 micro g/mL. However, the cytotoxic activity was not correlated with the radical intensity of the fractions. Three 70% MeOH extract fractions (70M2-4) produced radical and efficiently scavenged the O(2)(-) produced by hypoxanthine and xanthine oxidase reaction. All of the fractions tested were not effective for anti-H. pylori and anti-HIV. Fractions H3 and H4 of hexane extract, and M2 and M3 of MeOH extract showed a remarkable MDR reversal activity comparable with that of (+/-)-verapamil (a positive control). These results indicate the therapeutic value of persimmon peel extracts as potential antitumor and MDR-reversing agents.     

In vivo antitumor activity of pegylated zinc protoporphyrin: targeted inhibition of heme oxygenase in solid tumor

High expression of the inducible isoform of heme oxygenase (HO-1) is now well known in solid tumors in humans and experimental animal models. We reported previously that HO-1 may be involved in tumor growth (Tanaka et al., Br. J. Cancer, 88: 902-909, 2003), in that inhibition of HO activity in tumors by using zinc protoporphyrin (ZnPP) significantly reduced tumor growth in a rat model. We demonstrate here that poly(ethylene glycol)-conjugated ZnPP (PEG-ZnPP), a water-soluble derivative of ZnPP, exhibited potent HO inhibitory activity and had an antitumor effect in vivo. In vitro studies with cultured SW480 cells, which express HO-1, showed that PEG-ZnPP induced oxidative stress, and consequently apoptotic death, of these cells. Pharmacokinetic analysis revealed that PEG-ZnPP-administered i.v. had a circulation time in blood that was 40 times longer than that for nonpegylated ZnPP. More important, PEG-ZnPP preferentially accumulated in solid tumor tissue in a murine model. In vivo treatment with PEG-ZnPP (equivalent to 1.5 or 5 mg of ZnPP/kg, i.v., injected daily for 6 days) remarkably suppressed the growth of Sarcoma 180 tumors implanted in the dorsal skin of ddY mice without any apparent side effects. In addition, this PEG-ZnPP treatment produced tumor-selective suppression of HO activity as well as induction of apoptosis. The major reason for tumor-selective targeting of PEG-ZnPP is attributed to the enhanced permeability and retention effect that is observed commonly in solid tumors for biocompatible macromolecular drugs. These findings suggest that tumor-targeted inhibition of HO activity could be achieved by using PEG-ZnPP, which induces apoptosis in solid tumors, probably through increased oxidative stress.     

Quantitative assessment of contaminating tumor cells in autologous peripheral blood stem cells of B-cell non-Hodgkin lymphomas using immunoglobulin heavy chain gene allele-specific oligonucleotide real-time quantitative-polymerase chain reaction

A real-time quantitative-polymerase chain reaction (RQ-PCR) targeting the immunoglobulin heavy chain (IgH) gene has been used for the quantification of minimal residual disease (MRD) in B-cell hematological malignancies. In non-Hodgkin lymphoma (NHL), experimental costs are increased, as a large number of primer-probe sets are required because of diversity, due to somatic and ongoing mutations of the IgH gene. We developed an allele-specific oligonucleotide (ASO) combined with a germline consensus probe-based RQ-PCR assay and examined MRD in peripheral blood stem cells (PBSC). The IgH consensus probes were adapted in seven (50%) of 14 amplifiable cases. Patients with heavily contaminating tumor cells in PBSC relapsed after PBSC transplantation. Our strategy will contribute to the development of a cost-efficient, precisely quantitative and systemic detection assay for MRD in NHL.     

Targeted gene delivery to human osteosarcoma cells with magnetic cationic liposomes under a magnetic field

Gene delivery using cationic liposomes results in relatively low transfection, especially under in vivo conditions. This system, however, can overcome some of the problems associated with viral delivery systems. The present study was carried out in order to improve the transfection efficiency of cationic liposomes by preparing magnetic cationic liposomes (MCL). Small MCL approximately 40 nm in diameter and incorporating one or two magnetite particles were prepared with phosphatidylethanolamine and 3beta-[N-(N', N'-dimethylaminoethane)-carbamoyl] cholesterol. The efficiency of MCL in gene delivery was evaluated by using plasmid DNA containing a luciferase reporter gene and human osteosarcoma Saos-2 cells. Without a magnetic field, maximum luciferase activity was observed when DNA was mixed with MCL at a 1:5 ratio and incubated with cells for 6 h. Under a magnetic field, maximum luciferase activity was achieved by 30-min magnetic induction. This improvement in transfection efficiency by magnetic induction was approximately 3.5-fold. The feasibility of this active transgenic system was further shown by measuring apoptosis rates after transfection of the p53 gene to Saos-2 cells. Apoptosis rates increased to 18.9% from 2.4% by magnetic induction. In conclusion, a gene delivery system including MCL and magnetic induction was found to achieve rapid and enhanced gene delivery in vitro. Such a gene delivery system may be applicable under in vivo conditions, and is expected to offer numerous clinical advantages.     

Pre- and post-operative adjuvant chemotherapy in colorectal cancer

A multi-center randomized controlled study was conducted in order to investigate the usefulness of pre- and post-operative adjuvant chemotherapy in colorectal cancer. The patients were stratified into those with colon cancer and those with rectal cancer and divided into 2 groups, Group A and Group B. The patients in Group A received tegafur suppositories (750 mg/day) from 1 to 2 weeks prior to surgery, to 2 weeks following surgery and then oral administration of tegafur and uracil (UFT) (260 mg/m(2)) for 1 year. The patients in Group B, on the other hand, received only UFT (260 mg/m(2)) for 1 year beginning week 2 after surgery. Although there was no significant difference between Groups A and B in the 5-year survival rate, the 5-year disease-free survival rate was significantly higher in Group A, especially for rectal cancer (p<0.05). In addition, remote metastases tended to be suppressed for both colon and rectal cancer in Group A (p=0.08 and p=0.072). There was no serious adverse reaction to tegafur. Pre- and post-operative adjuvant chemotherapy with tegafur had fewer adverse reactions and was convenient to administer. Thus, it was considered useful for suppression of postoperative distant metastasis in colorectal cancer.